Neuroscience
-
Neonatal treatment of rat pups with clomipramine (CLI) has been shown to cause long-lasting and persistent depression-related behaviors and changes in sleep architecture and in brain-derived neurotrophic factor (BDNF) signaling in adult animals, producing an animal model of depression. However, the molecular mechanisms which mediate these effects of early-life CLI treatment on adult animals remain largely unknown. In order to characterize these further, we investigated in neonatally CLI-treated rats the sleep architecture as well as the extracellular and cellular levels of sleep regulators (nitric oxide, adenosine) and BDNF, respectively, in the basal forebrain (BF), i.e. the brain area which is implicated in sleep and depression. ⋯ At the molecular level, the normal homeostatic response was dissociated: the rise in the adenosine level was not accompanied by a rise in the nitric oxide concentration. Moreover, while BF BDNF levels decreased during SD in control rats, such a decline was not observed in CLI rats. Taken together, neonatal CLI treatment produces long-lasting functional changes in the sleep architecture and sleep regulation in adult rats, accompanied by dysregulated BDNF signaling in the BF.
-
In this study, we investigated effects of intra-central amygdala (intra-CeA) administrations of a cannabinoid agonist, WIN55,212-2 by itself and its interaction with β1-adrenoceptor agents on memory consolidation. We used a step-through inhibitory avoidance (IA) task to assess memory in male Wistar rats. The results showed that post-training intra-CeA administrations of different doses of WIN55,212-2 at doses of 0.1 and 0.25 μg/rat impaired memory consolidation (or induced amnesia) as revealed by a decrease in step-through latency on the test day. ⋯ Although, post-training intra-CeA administrations of β1-adrenoceptor antagonist, atenolol alone at different doses (0.01, 0.025, 0.05 and 0.1 μg/rat) had no significant effect, but its co-administrations at doses of 0.05 and 0.1 μg/rat along with an ineffective dose of WIN55,212-2 (0.05 μg/rat) induced amnesia, and at dose of 0.1 μg/rat along with an effective dose of WIN55,212-2 (0.25 μg/rat) increased amnesia that induced by the later drug. Moreover, the improving effect of isoprenaline (0.025 μg/rat) on amnesia induced by WIN55,212-2 (0.25 μg/rat) was prevented by intra-CeA co-injections of atenolol at doses of 0.01 and 0.025 μg/rat. The present results suggest that a β1-adrenoeceptor mechanism in the central amygdala (CeA) is involved in amnesia induced by post-training intra-CeA injections of WIN55,212-2.
-
It has been reported that central chemoreceptor cells in the medulla are distributed in close apposition to capillary blood vessels in the medulla. Phox2b-expressing neurons in the retrotrapezoid nucleus (RTN) respond to high CO(2)/H(+) stimulation and have been suggested to play an important role in central chemoreception. In newborn rats, the RTN overlaps at least partially with the parafacial respiratory group (pFRG), which consists predominantly of preinspiratory neurons. ⋯ We showed that Phox2b-ir neurons in the parafacial region of the rostral ventral medulla tended to assemble around capillary blood vessels. We also confirmed that pFRG/preinspiratory neurons that were sensitive to hypercapnic stimulation in the presence of tetrodotoxin were Phox2b-ir neurons and were tightly apposed to the blood vessels along the longitudinal axis. Our findings suggested that the location of Phox2b-ir neurons, including preinspiratory neurons of the pFRG, matched their role as sensors of blood CO(2) concentration.
-
Intermittent social defeat stress exposure augments behavioral response to psychostimulants in a process termed cross-sensitization. Brain-derived neurotrophic factor (BDNF) mediates synaptic plasticity and cellular responses to stress and drugs of abuse. We previously showed that repeated social defeat stress persistently alters BDNF and activates ΔFosB expression in mesocorticolimbic regions. ⋯ Stress exposure increased BDNF immunoreactivity in anterior cingulate, prelimbic and infralimbic regions of the prefrontal cortex (PFC), medial amygdala (AMY), nucleus accumbens (NAc) and VTA; ΔFosB labeling in anterior cingulate cortex (ACG) and nucleus accumbens; and ΔFosB/BDNF co-expression in prelimbic cortex (PL), nucleus accumbens and medial amygdala. Infralimbic ΔFosB-labeling was enhanced by stress in neurons innervating the VTA. Increased ΔFosB/BDNF co-expression and persistent functional activation of corticolimbic neurons after stress may contribute to mechanisms underlying cross-sensitization to psychostimulants.
-
In the recent past, the pathogenesis of Parkinson's disease (PD) has evolved from a neurodegenerative disorder considered entirely sporadic to a disease with an unequivocal genetic component. Indeed, different inherited forms of PD have been discovered and characterized, although the functional roles of the gene products identified are still under intense investigation. ⋯ Although most of the rodent models display neither obvious behavioral impairment nor evidence for neurodegeneration, remarkable abnormalities of dopamine-mediated neurotransmission and corticostriatal synaptic plasticity have been described, indicative of a fundamental distortion of network function within the basal ganglia. The picture emerging from a critical review of recent data on monogenic parkinsonisms suggests that mutations in PD genes might cause developmental rearrangements in the corticobasal ganglia circuitry, compensating the dopaminergic dysfunction observed both in mice and humans, in order to maintain proper motor function.